A question of identity excites Thor

Neuron cells

Image: whitehoune/Adobe Stock

Image: whitehoune/Adobe Stock

When Professor Stefan Thor talks about genetically engineering ‘spare parts’ for humans, he is constantly referring to microscopic components, the cells.

Since high school, Professor Thor, a developmental
biologist at UQ’s School of Biomedical Sciences, has been fascinated by how cells in the body know their precise function.

“Our bodies are full of trillions of cells with thousands of different identities, all engaged in different roles,” Professor Thor explains.

“The question is: How do these cells know what identity they’re supposed to have?

“When I started my research in the late 1980s, we knew almost nothing about these processes, but the field has moved forward at tremendous speed.

“We now understand more and more about the elaborate regulatory pathways playing out during embryogenesis.

“Cells are first told what particular team to belong to
– whether they should be part of the muscle system or nervous system for example – and are sub-allocated different tasks as development proceeds.

“It is a sequential process with finer and finer instructions and finally cells acquire their terminal identity.

“Our studies in fruit flies have demonstrated that combinations of genes, rather than one single gene at a time, operate together to tell cells what they should be. This ‘combinatorialism’ explains how hundreds of regulatory genes can generate thousands of different cell identities.”

Now researchers can grow human stem cells in a dish, and drive them into dfferent terminal cell identities, like muscle or nerve cells. The long-term goal is to even create complete human organs from a patient’s own cells.

“As a car gets older you are able to replace different parts,” Professor Thor says.

“The goal of many laboratories is now to make human ‘spare parts’, to replace the ones that fail as your body is getting older, or to add parts that were never generated in the first place in younger individuals.

Professor Thor began studying cells in fruit flies, but is now focused on the hypothalamus, a small structure in the centre of the human brain that contains hundreds of different cell types controlling many aspects of human physiology, including energy and fluid balance, thermoregulation, sleep wake states, stress responses, growth and reproduction, as well as emotional and social behaviours.

Hypothalamus

Hypothalamus (Image: mybox/Adobe Stock)

Hypothalamus (Image: mybox/Adobe Stock)

“This is one of the parts of the brain where we have the least understanding about how different cell types are made, so it is an interesting frontier,” Professor Thor says.

“The goal is to learn how different cell types are normally specified in the hypothalamus, and then apply that knowledge to human stem cells, and try and make particular spare parts.”

Professor Thor is keen to secure external funding to start his own research lab to study the hypothalamus, while continuing teaching students at UQ.

“Teaching at the university level is fascinating, because you are trying to convey some really complicated things to students … and when you can tell from the exams later that they understood these very complicated things, it is incredibly fulfilling,” he says.

Professor Thor undertook his PhD at Umea University in the north of Sweden before moving to San Diego, USA with his wife Osa to complete his post-doctoral training at the Salk Institute for Biological Studies.

From there, he set up his own lab at Harvard Medical School in Boston and spent five years building his own research team, before returning to Sweden after children Lucas and Frida were born.

In Sweden, he set up a new research team at Linkoping University, south of Stockholm, before moving to Australia and taking up a position at UQ.

“I’d been here a couple of times and loved it. It was always in the back of my mind we should live here and I managed to land a position at UQ,” Professor Thor says.

“Australia is welcoming to people from overseas and the system is very organised, so for us it has been an easy place to settle in.

"UQ is a large and dynamic university and it's exciting being here with the strong research going on in the biomedical field."

Professor Stefan Thor in lab

This is featured in the Winter 2021 edition of UQmedicine Magazine. View the latest edition here. Or to listen, watch, or read more stories from UQ’s Faculty of Medicine, visit our blog, MayneStream.